FoxA1 binding directs chromatin structure and the functional response of a glucocorticoid receptor-regulated promoter
S Belikov, C Åstrand, O Wrange�- Molecular and cellular biology, 2009 - Am Soc Microbiol
S Belikov, C Åstrand, O Wrange
Molecular and cellular biology, 2009•Am Soc MicrobiolReconstitution of the glucocorticoid receptor (GR)-regulated mouse mammary tumor virus
(MMTV) promoter in Xenopus oocytes was used to monitor the effects of different
transcription factor contexts. Three constitutively binding factors, nuclear factor 1 (NF1),
octamer transcription factor 1 (Oct1), and the Forkhead box A1 (FoxA1), were shown to act in
concert, to direct the chromatin structure, and to enhance the GR response. FoxA1 has a
dominant effect in the absence of hormone and induces a cluster of DNase I-hypersensitive�…
(MMTV) promoter in Xenopus oocytes was used to monitor the effects of different
transcription factor contexts. Three constitutively binding factors, nuclear factor 1 (NF1),
octamer transcription factor 1 (Oct1), and the Forkhead box A1 (FoxA1), were shown to act in
concert, to direct the chromatin structure, and to enhance the GR response. FoxA1 has a
dominant effect in the absence of hormone and induces a cluster of DNase I-hypersensitive�…
Abstract
Reconstitution of the glucocorticoid receptor (GR)-regulated mouse mammary tumor virus (MMTV) promoter in Xenopus oocytes was used to monitor the effects of different transcription factor contexts. Three constitutively binding factors, nuclear factor 1 (NF1), octamer transcription factor 1 (Oct1), and the Forkhead box A1 (FoxA1), were shown to act in concert, to direct the chromatin structure, and to enhance the GR response. FoxA1 has a dominant effect in the absence of hormone and induces a cluster of DNase I-hypersensitive sites in the segment comprising bp− 400 to+ 25. This FoxA1-mediated chromatin remodeling does not induce MMTV transcription, as opposed to that of the GR. However, the robust FoxA1-dependent chromatin opening has the following drastic functional consequences on the hormone regulation:(i) GR-DNA binding is facilitated, as revealed by dimethyl sulfate in vivo footprinting, leading to increased hormone-induced transcription, and (ii) the GR antagonist RU486 is converted into a partial agonist in the presence of FoxA1 via ligand-independent GR activation. We conclude that FoxA1 mediates a preset chromatin structure and directs a context-specific response of a nuclear receptor. Furthermore, the alternative nucleosome arrangement induced by GR and FoxA1 implies this to be determined by constitutive binding of transcription factors rather than by the DNA sequence itself.
![](https://cdn.statically.io/img/scholar.google.com/scholar/images/qa_favicons/asm.org.png)